Loss of association between plasma irisin levels and cognition in Alzheimer's disease. (February 2022)

• Record Type: Journal Article
• Authors: Kim, Keun You; Kwak, Seyul; Ha, Junghee; Oh, Dae Jong; Kim, Minae; Cho, So Yeon; Kim, Hyunjeong; Lee, Jun-Young; Kim, Eosu
• Is Part Of: Psychoneuroendocrinology. Volume 136(2022)
• Publication Date: 2022-02
• Subjects: AD Alzheimer's disease -- BDNF brain-derived neurotrophic factor -- CSF cerebrospinal fluid -- MRI magnetic resonance imaging -- CDR Clinical Dementia Rating -- HbA1c hemoglobin A1c -- MMSE Mini-Mental State Examination -- CERAD-K Korean version of the Consortium to Establish a Registry for Alzheimer's Disease -- MCI mild cognitive impairment -- CN cognitively normal -- DSM-IV-TR Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision -- CDR-SB Clinical Dementia Rating-Sum of Boxes -- SGDS Short form of Geriatric Depression Scale in Korean version -- TMT-A Trail Making Test A -- TMT-B Trail Making Test B -- APOE4 apolipoprotein E4 -- WMHL white matter hyperintensity lesions -- ELISA enzyme-linked immunosorbent assay -- GM gray matter -- WM white matter -- ROIs regions of interest -- TIV total intracranial volume -- FLAIR fluid-attenuated inversion recovery -- ACG anterior cingulate gyrus -- STG superior temporal gyrus -- IFG inferior frontal gyrus -- ANOVA analysis of variance -- BMI body mass index -- HOMA-IR Homeostatic Model Assessment for Insulin Resistance -- CNS central nervous system; Irisin -- Cognition -- Brain volume -- Alzheimer's disease -- Diabetes; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2021.105624
• Languages: English
• ISSNs: 0306-4530

Abstract

Abstract: Background: Irisin, an exercise-induced myokine, has been shown to have beneficial effects on cognitive and metabolic functions. However, previous studies assessing the levels of circulating irisin in patients with Alzheimer's disease (AD) or diabetes mellitus (DM) have provided inconsistent results. This suggests that the normal physiological action of irisin may be altered by disease-associated pathological conditions in target organs. Objective: To investigate the association of plasma levels of irisin with cognition and brain structures according to the presence or absence of AD and DM. Methods: Plasma levels of irisin, multi-domain cognition, and volumes of relevant brain regions were assessed using enzyme-linked immunoassay, neuropsychological test, and magnetic resonance imaging, respectively. We classified 107 participants by cognitive (cognitively normal [CN, n = 23], mild cognitive impairment [MCI, n = 49], and AD [n = 35]) and metabolic (non-DM [n = 75] and DM [n = 32]) states. Results: Disease state-stratified multiple regression analyses showed that plasma levels of irisin were positively associated with cognition only in participants without AD (CN plus MCI). By contrast, in participants with AD, these associations lost significance, and furthermore, higher levels of irisin indicated smaller hippocampal, superior temporal, and inferior frontal volumes. The association between plasma irisin levels and cognition was not affected by the presence of DM. Consistently, moderation analysis revealed that the relationship between plasma irisin levels and cognition or brain structures was significantly modified by the presence of AD, not that of DM. Conclusion: Our findings suggest that the beneficial actions of circulating irisin on cognition may be attenuated by AD-induced pathological conditions in the brain. Highlights: Alzheimer's disease alters the relationship of irisin with cognition and brain volume. Diminished beneficial effect of irisin in Alzheimer's disease supports "irisin resistance." Relation of irisin to cognition and brain volume is unaffected by diabetes mellitus.